OP0063 OLOKIZUMAB IMPROVES PATIENT REPORTED OUTCOMES IN MODERATE TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS PATIENTS INADEQUATELY CONTROLLED BY METHOTREXATE (MTX-IR): RESULTS FROM THE PHASE 3 RANDOMIZED CONTROLLED TRIAL, CREDO 2
Authors: V. Strand, E. Choy, E. Nasonov, T. Lisitsyna, A. Lila, S. Kuzkina, M. Samsonov, E. Feist
Journal: Annals of the Rheumatic Diseases (2022)

Background Olokizumab (OKZ) is an interleukin-6-inhibitor for treatment of Rheumatoid Arthritis (RA). In these analyses, we present patient reported outcomes (PROs) reported by MTX-IR patients with moderate to severely active RA treated with OKZ vs adalimumab (ADA) or placebo in a phase 3 randomized controlled trial (RCT) (ClinicalTrials.gov number, NCT02760407 ). Objectives To assess the effect of OKZ treatment compared with placebo and ADA in patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), fatigue (FACIT-F) and health related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores) and work participation (WPS-RA) at week 12. Methods 1648 patients receiving MTX were randomized to receive SQ injections: 1) OKZ 64 mg every 2 weeks (q2w, n=464), 2) OKZ 64 mg q4w (n=479), 3) ADA 40 mg q2w (n=462) and 4) placebo q2w (n=243). At week 14, non-responders: subjects without ≥ 20% improvements in both swollen and tender joint counts, added rescue medication (sulfasalazine and/or hydroxychloroquine) to study treatment. Between groups differences in least-squares mean (LSM) changes from baseline were analyzed. Results At week 12, treatment with both OKZ doses and ADA resulted in statistically greater LSM changes from baseline than placebo across all PROs, including 7 of 8 domains of SF-36 with exception of role emotional (Table 1 and Figure 1). Reported work and household work impairments, days productivities were reduced by half and missed household work days because of arthritis were all improved (p&lt;0.01) with OKZ and ADA treatment. PROs further improved to week 24 in the active treatment arms. Post hoc analyses demonstrated that a higher proportion of patients receiving both doses of OKZ as well as ADA reported improvements ≥ minimum clinically important differences vs placebo (p&lt;0.01) across all PROs, indicating clinically meaningful benefits on an individual patient basis. Estimates of numbers needed to treat indicated that between 5 and 10 patients would need to be treated to achieve these benefits. More patients in both OKZ groups reported scores ≥ normative values in PtGA, HAQ-DI and SF-36 PCS scores; with ADA in PtGA and HAQ-DI. Table 1. Mean baseline PROs and LSM changes to week 12 Baseline, mean (standard deviation) 12 weeks LSM changes (standard error) OKZ q2w, N=464 OKZ q4w, N=479 ADA q2w, N=462 Placebo, N=243 OKZ q2w, N=464 OKZ q4w, N=479 ADA q2w, N=462 Placebo, N=243 PtGA-VAS 67.5(20.2) 66.8(20.9) 66.7(21.0) 67.4(20.0) -29.7(1.1)# -29.5(1.0)# -31.6(1.1)# -21.0(1.5) Pain-VAS 68.4(20.6) 67.1(21.0) 66.8(21.5) 66.5(20.7) -31.8(1.1)# -31.7(1.1)# -32.7(1.1)# -21.3(1.6) HAQ-DI* 1.7(0.58) 1.7(0.60) 1.7(0.57) 1.7(0.62) -0.6(0.03)# -0.6(0.03)# -0.6(0.03)# -0.4(0.04) Comparison vs. ADA LSM difference [97.5% CI] -0.03 [-0.12;0.05] 0.00 [-0.08;0.08] SF-36 PCS 31.8(7.0) 31.6(7.2) 31.4(7.4) 31.9(7.5) 8.1(0.4)# 7.8(0.4)# 8.1(0.4)# 4.9(0.5) SF-36 MCS 42.9(11.4) 43.50(11.3) 44.1(11.4) 43.1(11.0) 5.1(0.4) † 4.9(0.4) † 5.0(0.4) † 3.1(0.6) FACIT-F 26.7(10.7) 27.3(10.4) 27.4(11.3) 27.3(10.2) 8.4(0.4)# 8.1(0.4 )ⱡ 8.9(0.4)# 5.2(0.6) Footnotes: LSM difference (SE) 97.5% CI by ANCOVA. NRS imputation. *, secondary endpoint; †p≤0.05, ⱡp&lt;0.01, #p&lt;0.001 vs placebo; VAS (mm). Figure 1. SF-36 domain changes from baseline to week 12. *p≤0.05, **p&lt;0.01, ***p&lt;0.001 ADA vs placebo; *p≤0.05, **p&lt;0.01, ***p&lt;0.001 OKZ q2w vs placebo; *p≤0.05, **p&lt;0.01, ***p&lt;0.001 OKZ q4w vs placebo. AGNorms, age- and gender-matched; BL, baseline. Conclusion Treatment with both doses of OKZ resulted in similar, statistically significant improvements across PROs vs placebo in MTX-IR patients with moderate to severely active RA, comparable to ADA, that were clinically meaningful. Acknowledgements R-Pharm funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Disclosure of Interests Vibeke Strand Consultant of: Abbvie, Amgen, Arena, AstraZeneca, Bayer, BMS, Boehringer, Ingelheim, Chemocentryx, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Inmedix, Janssen, Kiniksa, Lilly, Novartis, Pfizer, Regeneron, Rheos, R-Pharm, Samsung, Sandoz, Sanofi, Scipher, Servier, Setpoint, Sorrento, Spherix, UCB, Ernest Choy Consultant of: Abbvie, Amgen, Bristol Myer Squibbs, Chugai Pharma, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, RPharm, Roche, Sanofi, and UCB., Grant/research support from: Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi and UCB, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Tatiana Lisitsyna: None declared, Alexander Lila Consultant of: Abbvie, Amgen, Bayer, Biotechnos, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, RPharm, Roche, Sanofi, Stada, Viatris and UCB, Sofia Kuzkina Employee of: R-Pharm, Mikhail Samsonov Employee of: R-Pharm, Eugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer.